Ten years ago, scientists discovered that they could restore some vision to blind mice by cell transplantation. This watershed moment ushered in a golden era of stem cell research focused on treating blindness. Today, a surprising discovery offers a new explanation about how vision restoration occurs. Previously, scientists thought that stem cell transplantation worked by simply replacing old, damaged cells with fresh, functioning stem cells. Dr. Valerie Wallace’s research upends this explanation. Her paradigm-shifting study demonstrates that transplanted stem cells do not replace old ones, but rather transfer their material into existing cells.

At the Foundation Fighting Blindness (FFB), we follow stem cell research developments very closely and carefully. Over the years, we have been inspired by the growing amount of evidence that shows it is possible to restore biological vision through cell transplantation. These research triumphs sometimes draw attention to areas that we don’t understand. For example, recent discoveries have improved our understanding of why many cells don’t survive the transplantation process. Last year, we were thrilled when FFB-funded scientist, Dr. Brian Ballios, restored partial vision to blind mice with the aid of a biomaterial, which significantly increased the survival rate of transplanted cells. Yet, even with the biomaterial, the transplantation process is still inefficient.

Why is it so hard to get transplanted photoreceptor cells to survive? What happens to cells after they are transplanted? Dr. Wallace’s discovery helps to answer this question, which has long evaded scientists. Her FFB-funded research team has been focused on trying to get cone photoreceptor cell transplantation to work. To do this, her team recently developed an innovative tool that allows them to closely follow transplanted cones with a fluorescent marker. This new cell-tracking tool offered a fresh perspective about what happens to stem cells after they are transplanted. They found that, contrary to popular belief, transplanted stem cells don’t integrate or mix with cells in the eye. Instead, they transfer some of their cellular material (including the fluorescent marker) to other cells that are already in the eye. Two other studies published in the journal Nature Communications, led by Dr. Robin Ali and Dr. Marius Ader, arrived at the same conclusion for rod photoreceptors.

Dr. Wallace’s findings, published today in the prestigious journal Stem Cells, are indeed paradigm shifting in the race to restore sight through stem cell transplantation. Moreover, this discovery is poised to impact the entire field of regenerative medicine. The implications are huge because so many research teams are conducting stem cell transplantation experiments that rely on fluorescent markers to measure success. Now, when scientists see fluorescent “donor” cells – they can no longer simply conclude that the donor cells have integrated into the host. Additional steps must be taken to confirm cellular identity.

Thanks to Dr. Wallace’s discovery, stem cell researchers have a new way to focus in on the problem of cell survival and cell integration. Dr. Wallace’s team has shown that this transfer also happens with proteins that are needed for vision, thus the vision rescue reported following transplantation might result from this material exchange phenomenon.

Dr. Wallace is most excited about the potential implications of this experiment: “We have stumbled upon a mode of communication between photoreceptors that advances how we understand the outcome of cell transplantation and that also has the potential to be exploited for therapeutic strategies.”She is already thinking about how this new knowledge can be used to develop new therapies, asking: “What if we could use this cellular exchange mechanism to deliver useful proteins to protect photoreceptors?”

Thanks to the FFB’s generous donors, we are proud to have funded many important stem cell discoveries, including this latest one by Dr. Wallace’s team. Many of these donors are affected by blindness. Many of them have a child or a parent who is losing their vision. The day that treatments become a reality can’t come soon enough. However, what these studies highlight is that the benefits of cell transplantation, if carried out today, would only be temporary because this transfer mechanism would degrade over time, which may lead to failed clinical trials and greater setbacks on the road to therapy. Discoveries that fill in gaps in our understanding of how cell transplantation works, instead of slowing progress, will actually lead to the development of better, safer and more effective therapies.

Our Director of Research & Education, Dr. Mary Sunderland, discussed the discovery in additional detail during a recent Facebook Live broadcast: